Studies regarding Fl mice provide valuable information regarding the influence of an immunologically heterozygous host on various aspects of disease. Results presented here demonstrate that T-cell lines obtained from SJL/J X PL/J (Fl) mice immunized with myelin basic protein (MBP) fragment 1-20 passively transferred experimental allergic encephalomyelitis (EAE) into naive Fl recipient mice. Splenic T-cells obtained from recipient mice after relapses could be cultured with either PL of Fl macrophages and passively transfer EAE. However, the same splenic T-cells cultured with SJL macrophages failed to transfer the disease. The expression of both parental la haplotypes (las and lau) by splenic macrophages was observed after treatment with interferon-gamma (IFN-gamma). However, a significantly greater degree of proliferation was obtained when Fl lymphocytes were incubated with either: (a) peptide fragment 120 as opposed to 9O-lOl; or (b) PL macrophages as opposed to SJL macrophages. The lack of a codominant response in the animals thus does not appear to be related to a variable degree of la haplotype expression,. The preferential response to lau and fragment 1-20 may be due to the strong interaction (high association constant) between lau and this antigenic determinant. Experiments examining the role of IL-2 receptor-bearing cells in EAE demonstrated that treatment of mice with the chimera protein, IL-2-PE40, inhibited inflammation, demyelination, and clinical manifestations of adoptively transferred EAE.